tbuckley/cabot-search huggingface dataset:
Patients' preferences for adjuvant osimertinib in non–small cell lung cancer (NSCLC) after complete surgical resection: What makes it worth it to patients? (PATT)—The Roswell Park (RP) Comprehensive Cancer Center experience.
Authors: Angel Mier-Hicks, Kristopher Attwood, Kayla Catalfamo, Prantesh Jain, Hongbin Chen, Edwin Yau, Amy P. Early, Grace K. Dy
Journal: Journal of Clinical Oncology (2022)

8520 Background: There are clinical controversies surrounding the US FDA approval of Osimertinib in December 2020 as adjuvant therapy, based on disease-free survival (DFS) improvement in patients (pts) with surgically resected stage IB-IIIA EGFRm NSCLC. We initiated a survey study to investigate our hypothesis that DFS benefit alone even without significant OS maybe deemed a valuable endpoint to pts after considering trade-offs. Methods: Participants were recruited from pts seen at the RP Thoracic Clinic from 01/21 to 12/21. Eligible pts who were being evaluated for adjuvant systemic therapy following surgical resection were given a self-administered survey based on the validated questionnaire by Blinman et al, which was modified to provide explanation of the differences between OS and DFS and the ADAURA trial results. Survey responses were collected in an online repository. Associations between survey responses and demographics were assessed using Fisher’s exact test. Changes in preference responses were assessed using McNemar’s test. Results: A total of 524 pts with NSCLC were screened, of which 101 pts were eligible to receive the survey. 51 pts (50%) responded to the survey. Median age of respondents was 69yrs (37-83), majority were female (69%, n = 35,), married (61%, n = 31), retired ( 63%, n = 32), had at least some college or higher education level(54%, n = 28), with history of smoking (84%, n = 43) and with stage IIIA (43%, n = 22) adenocarcinoma (80%, n = 41). To evaluate toxicity-related tradeoffs (Q1), a ≥12 mo. improvement in OS benefit was needed for 66% of pts to consider adjuvant Osi. However, an increase of ≥ 6 mo. of DFS was enough for 66% of pts to justify taking a daily medication (Q2). One mo. increase in DFS or OS was not enough for 60% and 78% of pts respectively to justify taking the medication. A threshold 1% increase in 5-year OS was sufficient to persuade patients to take Osi for three years, even with respect to toxicity side effects (p = 0.023). (Q3). Finally, in the hypothetical cost-based scenario (Q4), there was no indication that pts were willing to pay more for each incremental increase in OS. There appears to be some association between employment status (p =.033) or educational degree (p =.049) for tolerance of side effects if there is at least 1 additional year of DFS or OS. Conclusions: We observed that the value patients ascribe to adjuvant Osimertinib is influenced by factors besides efficacy. Knowing pts' preferences for cancer treatments can better inform regulatory bodies in formulating cost-sharing structure for cancer therapies. Our study highlights the importance of shared decision making based on individual pts' preferences.
Identification and genome-wide profiling of TET1-overexpressing prostate cancer reveal a collective activation of zinc-finger transcription factors and zinc-finger anti-viral proteins
Authors: U. Schagdarsurengin, C. Luo, H. Slanina, D. Sheridan, S. Fuessel, S. Gattenloehner, N. Böğürcü-Seidel, G. Baretton, L.C. Hofbauer, F. Wagenlehner, T. Dansranjav
Journal: European Urology (2022)
SARS-CoV-2 seroprevalence in the adult detainees of the Paris area in 2021: A multicenter cross-sectional study
Authors: Guillaume Mellon, Alexandra Rouquette, Catherine Fac, Béatrice Carton, François Cordonnier, Emmanuelle David, Béatrice Goutte, François Heulin, Valérie Kanoui, Ludovic Levasseur, Pascale Racle, Benjamin Silberman, Kawther Nehri, Anne Dulioust, Anne-Marie Roque-Afonso
Journal: Journal of Infection (2022)
Head to head comparison between off-clamp vs on-clamp RAPN in high-risk RENAL score kidney tumors
Authors: R.S. Flammia, U. Anceschi, A. Tufano, G. Tuderti, C. Fiori, J. Lee, A. Minervini, U. Capitanio, D. Eun, R. Autorino, F. Porpiglia, M. Gallucci, C. Leonardo, G. Simone
Journal: European Urology (2022)
The real-world experience of adjuvant docetaxel and cyclophosphamide (TC) chemotherapy in HER-2 negative breast cancer.
Authors: Danilo Giffoni M. M. Mata, Kelvin K. Chan, Andrea Eisen, Rossanna C. Pezo, Ines B. Menjak, Maureen E. Trudeau
Journal: Journal of Clinical Oncology (2022)

538 Background: Adjuvant chemotherapy in breast cancer (BC) substantially improves overall survival (OS) and the risk of recurrence. The short and long-term side effects of anthracycline, and its modest benefits in the adjuvant setting, led to controversy about its role in comparison with TC. We aim to compare the OS of TC with anthracycline-based regimens in Ontario, the most populous province in Canada. Methods: We conducted a retrospective population-based cohort study using the Institute for Clinical Evaluative Sciences (ICES) database, involving females with stage I-III BC HER2-negative. Patients were treated with adjuvant chemotherapy between January 2009 to December 2017. The anthracycline regimens for comparison were as follows, FEC-D: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Docetaxel; and ACT: Doxorubicin, Cyclophosphamide, followed by Docetaxel or Paclitaxel. Exclusion criteria included missing baseline characteristics, a prior history of malignancy or chemotherapy starting more than 120 days from breast surgery. The end of follow-up was March 31 st , 2018. Adjusted analyses to compare OS by positive axillary lymph nodes (LN) and chemotherapy regimens were conducted with Cox proportional hazards models. Results: Of a total 10634 female patients with BC, 60% were ≥ 50 years-old, with 19.6% stage I, 61.1% stage II, and 19.3% stage III and 7130 (67%) women were classified as ER+ and 2379 (22.4%) as ER-. Among 5764 (54.2%) patients with positive LN, 4300 (40.4%) had LN 1-3 and 1464 (13.8%) had LN ≥ 4. There were 4945 (46.5%) high-grade cases. There were 2487 (23.5%) patients treated with TC, 2981 (28%) with ACT, and 5166 (48.5%) with FEC-D. With a median follow-up of 5.5 years, the OS comparison for the entire study population showed hazard ratio (HR) of TC vs ACT was 1.47 (95% CI 1.14 – 1.90), p = 0.0027 and TC vs FEC-D HR was 1.48 (95% CI 1.18 – 1.86), p = 0.0007. For ER+ patients treated with TC, the OS comparison of LN 1-3 and LN ≥ 4 vs. LN 0 showed HR 1.34 (95% CI 0.81 – 2.21), p = 0.26, and HR 4.29 (95% CI 2.09 – 8.79), p &lt; 0.0001, respectively. For ER+ LN 0 patients, the OS HR of TC vs. ACT was 1.15 (95% CI 0.58 – 2.35), p = 0.67, and TC vs. FEC-D HR was 1.38 (95% CI 0.81 – 2.33), p = 0.23. For ER- patients treated with TC, the OS comparison of LN 1-3 and LN ≥ 4 vs. LN 0 showed HR 1.12 (95% CI 0.42 – 3.01), p = 0.82 and HR 4.41 (95% CI 1.33 – 14.59), p = 0.015, respectively. For ER- LN 0 patients, the OS HR for TC vs. ACT was 2.04 (95% CI 1.09 – 3.81), p = 0.025, and TC vs. FEC-D HR was 2.05 (95% CI 1.08 – 3.90), p = 0.028. Conclusions: Patients treated with adjuvant TC who had four or more axillary LN had significantly lower OS when compared to patients with LN 0. For women with ER- disease, TC demonstrated a significant unfavourable survival outcome when compared to anthracycline-based treatments.
Clinician approach to cardiopulmonary exercise testing for exercise prescription in patients at risk of and with cardiovascular disease
Authors: Flavio D'Ascenzi, Luna Cavigli, Antonio Pagliaro, Marta Focardi, Serafina Valente, Matteo Cameli, Giulia Elena Mandoli, Stephan Mueller, Paul Dendale, Massimo Piepoli, Matthias Wilhelm, Martin Halle, Marco Bonifazi, Dominique Hansen
Journal: British Journal of Sports Medicine (2022)

Exercise training is highly recommended in current guidelines on primary and secondary prevention of cardiovascular disease (CVD). This is based on the cardiovascular benefits of physical activity and structured exercise, ranging from improving the quality of life to reducing CVD and overall mortality. Therefore, exercise should be treated as a powerful medicine and critical component of the management plan for patients at risk for or diagnosed with CVD. A tailored approach based on the patient’s personal and clinical characteristics represents a cornerstone for the benefits of exercise prescription. In this regard, the use of cardiopulmonary exercise testing is well-established for risk stratification, quantification of cardiorespiratory fitness and ventilatory thresholds for a tailored, personalised exercise prescription. The aim of this paper is to provide a practical guidance to clinicians on how to use data from cardiopulmonary exercise testing towards personalised exercise prescriptions for patients at risk of or with CVD.
Benchmarking maintenance therapy survival in first-line advanced urothelial carcinoma using disease modeling.
Authors: Matt D. Galsky, Heidi Wirtz, Brian Bloudek, Zsolt Hepp, Jack Timmons, Enrique Lenero, Thomas Powles
Journal: Journal of Clinical Oncology (2022)

4575 Background: First-line (1L) maintenance avelumab (maintA) in patients with advanced urothelial carcinoma (aUC) prolonged overall survival (OS) in the JAVELIN Bladder 100 trial. JAVELIN measured OS from the initiation of maintA among a subgroup of the overall aUC 1L treated population, including only patients who did not progress with 1L platinum-based therapy (PBT) and remained progression free during a 4-10 week treatment-free interval following completion of 1L PBT. As such, patients who progressed on or immediately following PBT were not included in the trial. To address this, we used disease modeling to estimate maintA OS measured from initiation of 1L PBT to align maintA OS with the common initiation point to benchmark with other 1L clinical trials. Methods: We developed a simulated cohort to estimate OS from initiation of 1L PBT in all aUC patients including those who received maintA. Eligibility for maintA (PBT progressed vs not progressed) was assessed at 5.6 months post-initiation of 1L PBT, accounting for 6 PBT cycles and a nominal 6-week treatment-free interval. Median OS of 14.3 months from the 1L PBT arm of a recent 1L trial, KEYNOTE-361, was used to represent the OS of the simulated cohort of 1L aUC patients. The simulated cohort was stratified by eligibility for maintA. Among the 1L treated population, 57% were projected to be progression-free and eligible for maintA based on progression-free survival (PFS) from KEYNOTE-361. Among those eligible, 85% were assumed to receive maintA based on expert clinical input. OS of maintA eligible patients was 21.4 months from JAVELIN. Our disease model estimated OS among a maintA ineligible simulated cohort, which was combined with the maintA eligible cohort to yield an estimated OS in the overall aUC population measured from initiation of 1L PBT. Results: Approximately 50% of the 1L modeled population receive maintA (i.e., 57% eligible x 85% treated). Our approach estimated a median OS of 9.9 months for the maintA ineligible cohort and 27.0 months for the maintA eligible cohort. Combined, the estimated median OS with maintA, measured from initiation of 1L PBT, in all 1L-treated aUC patients was 15.8 months (vs 14.3 months with PBT only in 1L). Conclusions: MaintA improves OS for eligible patients, however our simulation model suggests a significant proportion of patients will not receive MaintA. The estimated OS of 15.8 months for the population-level impact of maintA, accounting for patients ineligible for 1L maintA, demonstrates remaining unmet need in the overall 1L aUC population.
Using Charlson comorbidity index (CCI) to predict outcomes of older patients with acute promyelocytic leukemia (APL).
Authors: Prajwal Dhakal, Elizabeth Lyden, Avantika Pyakuryal, Manoj P. Rai, Vijaya Raj Bhatt
Journal: Journal of Clinical Oncology (2022)

e18751 Background: A large-scale study specifically analyzing an association between comorbidity burden and outcomes is lacking in APL. We hypothesized that a greater comorbidity burden independently predicts worse outcomes in patients ≥60 years with APL. Methods: We utilized the National Cancer Database to identify patients ≥60 years diagnosed with APL between 2004 and 2015. CCI scores were used to evaluate comorbidity burden, and patients were divided into 3 groups with CCI of 0, 1, and ≥2. We used chi-square test to determine association between CCI and different variables. Multiple logistic regression analyses and Cox regression models evaluated the effects of CCI on one-month mortality and overall survival (OS), respectively. Results: Of 2221 patients, 59% had CCI of 0, 27% had CCI 1, and 14% had CCI ≥2. Compared to patients with CCI 1 or CCI ≥2, a higher proportion of patients with CCI 0 had private insurance, and higher education and income status, were treated at academic centers, and received multiagent therapy. One-month mortality was 16%, 24%, and 32% for patients with CCI 0, 1, and ≥2, respectively. After adjusting for other co-variates, patients with CCI 0 had lower one-month mortality compared to CCI 1 (Odds ratio 1.67, 95% confidence interval [CI] 1.29-2.16, p &lt; 0.001) and CCI ≥ 2 (Odds ratio 2.31, 95% CI 1.70-3.13, p &lt; 0.001). Three-year OS was 61%, 53%, and 38% for patients with CCI 0, 1, and ≥2, respectively. After adjusting for other co-variates, OS was worse among patients with CCI 1 (Hazard ratio 1.27, 95% CI 1.10-1.46, p-value &lt; 0.001) and CCI ≥2 (Hazard ratio 1.74, 95% CI 1.48-2.06, p-value &lt; 0.001), compared to patients with CCI 0. Conclusions: Our study is among the first and the largest to examine an association between comorbidity burden and outcomes in older adults with APL. Greater comorbidity burden, indicated by higher CCI, predicted worse one-month mortality and OS, after adjusting for other co-variates. Thus, our study results establish CCI as an important and independent predictor of outcomes in APL. The study results can inform personalized estimates of mortality and OS based on comorbidity burden and facilitate treatment decision-making. Given the significant differences in outcomes of older adults based on comorbidity burden, future trials in APL should present comorbidity data and consider utilizing CCI to risk-stratify patients.
Relevance of digital rectal examination in presence of low PSA levels
Authors: C. Fede Spicchiale, M. Ambrosi Grappelli, L. Orecchia, G. D'Ippolito, A. Fasano, A. Turbanti, M. Podagrosi, S. Pletto, G. Farullo, E. Finazzi Agrò
Journal: European Urology (2022)
MEDB-23. Targeting epigenetic dysregulation in medulloblastoma with poor prognosis
Authors: Sara Badodi, Nicola Pomella, Xinyu Zhang, Nicolae Radu Zabet, M Albert Basson, Silvia Marino
Journal: Neuro-Oncology (2022)

Abstract Medulloblastoma (MB) is the most common paediatric malignant brain tumour and is classified into four distinct molecular subgroups (WNT, SHH, G3 and G4), each of them further subdivided into subtypes with different prognosis and responses to therapy. Deregulation of chromatin modifier genes play an essential role in MB, particularly in the G4 subgroup. A BMI1High;CHD7Low molecular signature identifies patients with poor survival within this subgroup. We show that BMI1High;CHD7Low sustains MB growth through regulation of MAPK/ERK signalling and via a novel epigenetic regulation of inositol metabolism in both G4 MB cells and patients. These tumours display over-activation of MAPK/ERK signalling, sustaining tumour proliferation, and of AKT/mTOR pathway which leads to energetic rewiring characterised by enhanced glycolytic capacity and reduced mitochondrial function. We demonstrate that inositol administration counteracts this metabolic alteration, impairs proliferation and significantly extends survival in a pre-clinical model. Moreover, inositol synergises with cisplatin, a chemotherapy agent currently used in MB treatment, enhancing its therapeutic effect in vivo. Additionally, we identify a synergistic vulnerability of BMI1High;CHD7Low MB to a combination treatment with BMI1 and MAPK/ERK inhibitors that overcomes acquired resistance to single-drug therapy. Mechanistically, we observe a CHD7-dependent binding of BMI1 to MAPK-regulated genes underpinning the CHD7-BMI1-MAPK regulatory axis that is critical for the anti-tumour effect of the inhibitors in vitro and in a pre-clinical model. Moreover, we demonstrate that the BMI1High;CHD7Low molecular signature defines G4 MB patients with an enhanced ERK1-ERK2 phosphorylation activity. Importantly, cerebellar neural stem cells modelling the BMI1High;CHD7Low signature are not affected by BMI1 and MAPK/ERK inhibitors and do not show metabolic adaptation hence are resistant to the proposed treatments. In summary, we have identified two actionable vulnerabilities in a pre-clinical setting modelling a molecularly defined group of MB patients, paving the way for the design of signature-matched clinical trials.
Coronary Artery Calcification Score and the Progression of Chronic Kidney Disease
Authors: Hae-Ryong Yun, Young Su Joo, Hyung Woo Kim, Jung Tak Park, Tae Ik Chang, Nak-Hoon Son, Tae-Hyun Yoo, Shin-Wook Kang, Suah Sung, Kyu-Beck Lee, Joongyub Lee, Kook-Hwan Oh, Seung Hyeok Han
Journal: Journal of the American Society of Nephrology (2022)

An elevated coronary artery calcification score (CACS) is associated with increased cardiovascular disease risk in patients with CKD. However, the relationship between CACS and CKD progression has not been elucidated.
Outcomes of hepatocellular carcinoma in obese patients: Insights from a nationwide database.
Authors: Umer Farooq, Diana Franco, Zahid Tarar, Faiz Anwer
Journal: Journal of Clinical Oncology (2022)

e16178 Background: Obesity is associated with hepatocellular carcinoma (HCC), affecting mortality and post-surgical outcomes. Growing epidemiological obesity trends parallel the constant rise of HCC incidence. Therefore, we sought to examine outcomes of HCC in obese patients. Methods: We investigated the National Inpatient Sample and National Readmission Database 2018-2019 using International Classification of Diseases-10 codes for adult patients with HCC. Analyses were performed using STATA (v 14.2), considering 2 sided P&lt; 0.05 as statistically significant. Proportions were compared using Fisher exact test and continuous variables using Student’s t-test. Confounding variables were adjusted using multivariate logistic and linear regression analyses. Results: Obese patients with HCC had lower odds of inpatient mortality and higher odds of hospice discharge ( P&lt; 0.05). Obesity was associated with a higher length of stay (LOS) by 0.90 days and hospital cost by 5,453 USD ( P&lt; 0.01). We found higher odds of acute renal failure (Adjusted odds ratio (aOR) 1.37, P&lt; 0.01) and a higher prevalence of HCV, smoking, and alcohol use in obese patients. There were no differences in lobectomy, partial hepatectomy, or transarterial radioembolization; however, higher odds of liver transplant were observed (aOR 1.82, P&lt; 0.01). A higher proportion of obese HCC patients had lymph nodes metastasis (6.43% vs. 6.08%, P:0.64). Rates of respiratory problems, ICU admission, cardiac arrest, HIV, DVT, myocardial infarction, and stroke were not different between the two groups ( P&gt; 0.05). Conclusions: Obese patients with HCC appear to have an advanced stage at presentation leading to lower rates of lobectomy, partial hepatectomy, and TARE and higher rates of liver transplant and hospice utilization. Future studies need to address the barriers leading to delays in diagnosis.[Table: see text]
Gemcitabine response prediction in the adjuvant treatment of resected pancreatic ductal adenocarcinoma using an AI histopathology platform.
Authors: Viswesh Krishna, Vivek Nimgaonkar, Ekin Tiu, Vrishab Krishna, Hriday Bhambhvani, Stephen Cook, Daniel Miller, Damir Vrabac, Anirudh Joshi, Aatur D. Singhi, Andrew Eugene Hendifar, Pranav Rajpurkar, Eric Andrew Collisson
Journal: Journal of Clinical Oncology (2022)

e16295 Background: Adjuvant chemotherapy improves survival following resection of pancreatic ductal adenocarcinoma (PDAC). A modified fluorouracil/irinotecan/oxaliplatin regimen (mFOLFIRINOX) has demonstrated improved disease free survival and overall survival, though gemcitabine-based monotherapy and gemcitabine plus capecitabine are alternatives in less fit patients. Though there are several proposed biomarkers to guide treatment decisions (GATA6, hENT1, and GemPred), no biomarker is used to guide treatment selection in clinical practice. Consequently, we sought to develop an artificial intelligence-derived signature of features from digital images of routine histopathology specimens that could identify patients susceptible to routine chemotherapeutic agents. Methods: 139 whole-slide digitized histological slides corresponding to 102 resected PDAC tumors from TCGA-PAAD were used in this study. This dataset corresponded to patients that had received either gemcitabine-backbone or 5 FU-backbone chemotherapy as their first-line adjuvant treatment. We extracted nuclei images from tissue regions using segmentation models and computed geometric features of these nuclei which we then correlated with Disease Specific Survival (DSS) in order to construct a signature associated with treatment benefit. This signature was compared against two board certified pathologists using the grade of the digital slides images to classify patients into above or below average DSS buckets. Results: Among quantitative geometric features, a set of area and ellipse features describing nuclei geometry correlated most with response to gemcitabine (R̃0.4). The cox proportional hazards model using these geometric nuclei features was found to be predictive of response to gemcitabine and achieved a C-index (95% CI) of 0.69 (0.58, 0.79). The pathologist-based baseline model for above and below average DSS had a median DSS of 443 and 461 days respectively. Using the average expected lifetime as the threshold, the model divides patients receiving gemcitabine into two histological subtypes with median DSS of 586 and 394 days respectively (p &lt; 0.05). The model appeared specific to gemcitabine. Among patients receiving 5-FU (n = 10) there was no statistical significance in median DSS between the subtypes and a c-index of 0.63 (0.27, 1.0). Conclusions: An artificial intelligence approach utilizing only routine histopathology can identify features that correlate with treatment outcomes in PDAC with classification performance (c-index:0.69) superior to the validated AJCC treatment prediction tool (0.59).
A ten-gene DNA-damage response pathway gene expression signature predicts gemtuzumab ozogamicin response in pediatric AML patients treated on COGAAML0531 and AAML03P1 trials
Authors: Mohammed O. Gbadamosi, Vivek M. Shastri, Abdelrahman H. Elsayed, Rhonda Ries, Oluwaseyi Olabige, Nam H. K. Nguyen, Angelica De Jesus, Yi-Cheng Wang, Alice Dang, Betsy A. Hirsch, Todd A. Alonzo, Alan Gamis, Soheil Meshinchi, Jatinder K. Lamba
Journal: Leukemia (2022)